Effect of Prograf (FK506) on spermatogenesis in rats

Hisatomi, Akitaka; Fujihira, Shiro; Fujimoto, Yoshikatsu; Fujii, Toshiyuki; Mine, Yasuhiro; Ohara, Kaname

doi:10.1016/0300-483x(96)03312-4

Cited by 30 publications

(26 citation statements)

References 11 publications

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“…Structural abnormalities in the testes and epididymis suggest that CsA may affect spermatogenesis and that tacrolimus has a direct action on the sperm in the epididymis. All these effects were reversible [58].…”

Section: The Immunosuppressed Fathermentioning

confidence: 98%

“…However, animal and human reports question the effects of immunosuppressants on male fertility [3,57,58]. Male rats receiving CsA 20 mg/kg/day from 2-3 to 120 days of age showed a significant decrease in testicular weight, sperm count, seminiferous tubular diameter, maturation, haploid cell population, circulating testosterone levels and number of offspring.…”

Section: The Immunosuppressed Fathermentioning

confidence: 99%

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In utero Exposure to Immunosuppressive Drugs

Prévot

Martini

Guignard³

2002

Neonatology

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The number of pregnant women receiving immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross the placenta, raising questions about the long-term outcome of the children exposed in utero. There is no higher risk of congenital anomalies. However, an increased incidence of prematurity, intrauterine growth retardation (IUGR) and generally low birth weight has been reported, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes.

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Section: The Immunosuppressed Fathermentioning

confidence: 98%

Section: The Immunosuppressed Fathermentioning

confidence: 99%

In utero Exposure to Immunosuppressive Drugs

Prévot

Martini

Guignard³

2002

Neonatology

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“…Few studies have been conducted to investigate the effects of FK-506 on the male reproductive system [Tai et al, 1994;Hisatomi et al, 1996]. In untreated female rats that mated with tacrolimus-treated male rats for 2 weeks, the number of live fetuses and the embryonic implantation index were reduced due to a decrease in the number and motility of the spermatozoa [Hisatomi et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

Caneguim

Cerri

Spolidório

et al. 2011

Cells Tissues Organs

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Treatment with tacrolimus (FK-506) has been shown to induce a significant decrease in the number of spermatocytes, spermatids, and Sertoli cells. Regarding the importance of the peritubular tissue for the maintenance of Sertoli cells, the integrity of the cellular and extracellular components of the peritubular tissue was evaluated in adult rats that were treated with 1 mg/kg/day of FK-506 for 30 and 60 days. Testicular sections were used for a quantitative analysis of the peritubular cells (PCs) and were submitted to the PAS method. Paraffin sections were submitted to the TUNEL method and to immunohistochemistry for the detection of caspase-3. Several testicular fragments were analyzed under a transmission electron microscope (TEM). A weak PAS reaction was noted in the peritubular tissue of the tacrolimus-treated animals. Next to the damaged peritubular tissue, the Sertoli cell nuclei were absent or dislocated from the basement membrane. In the treated animals, the number of PCs decreased significantly compared to the control animals, and these cells showed apoptotic features, were TUNEL positive, and were caspase-3 immunolabeled. Using the TEM, apoptosis was confirmed in myoid cells; moreover, the thickness and undulation of the basal laminae and an enlargement of the collagen I layer adjacent to the myoid cells was observed. Long-term treatment with the immunosuppressor induced peritubular myoid cell death by apoptosis and disarrangement of the peritubular extracellular layers. Future studies are necessary to confirm whether the structural alterations in the seminiferous epithelium are related to the effect of FK-506 on peritubular tissue.

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“…FK506, an immunosuppressant drug, binds to the PPIase active site to block PPIase activity, although FKBP52 binding to dynein in vitro is not inhibited by FK506 (Silverstein et al 1999). Still, FK506 has been shown to reduce sperm counts and motility in a rat model (Hisatomi et al 1996), suggesting FKBP52-dynein interactions in vivo. Consistent with a possible role for FKBP52-dynein interactions in sperm flagella, mice lacking functional dynein heavy chain (Dnahc1) show severe asthenozoospermia (Neesen et al 2001, Vernon et al 2005.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity

Hong¹,

Kim²,

Tranguch³

et al. 2007

Reproduction

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FKBP52 is a member of the FK506-binding family of immunophilins and serves as a co-chaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Male mice missing Fkbp52 are infertile, and this infertility has been ascribed to compromised sensitivity of the anterior prostate, external genitalia, and other accessory sex organs to androgen. Here, we show additional defects contributing to infertility. We found that epididymal Fkbp52 K/K sperm are sparse often with aberrant morphology, and they have reduced fertilizing capacity. This phenotype, initially observed in null males on a C57BL/6/129 background, is also maintained on a CD1 background. Expression studies show that while FKBP52 and androgen receptor are co-expressed in similar cell types in the epididymis, FKBP52 is also present in epididymal sperm flagella. Collectively, our results suggest that reduced number and abnormal morphology contribute to compromised fertilizing capacity of Fkbp52sperm. This study is clinically relevant because unraveling the role of immunophilin signaling in male fertility will help identify new targets for male contraceptives and/or alleviate male infertility. Reproduction (2007) 133 395-403

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Effect of Prograf (FK506) on spermatogenesis in rats

Cited by 30 publications

References 11 publications

In utero Exposure to Immunosuppressive Drugs

In utero Exposure to Immunosuppressive Drugs

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

Deficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity

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